Methods and systems for forming implants with selectively exposed mesh for fixation and related implants

ABSTRACT

Molded orthopaedic implants include at least one mesh substrate having opposing upper and lower primary surfaces. At least a major portion of the mesh substrate lower primary surface is integrally moldably attached to the molded implant body. The mesh substrate has at least one selectively exposed region devoid of molded material that exposes at least a portion of the mesh substrate upper surface to at least a partial thickness of the mesh substrate so as to allow for tissue in-growth in the at least one exposed region of the mesh substrate.

RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Ser. No. 60/885,682, filed Jan. 19, 2007, the contents of whichare hereby incorporated by reference as if recited in full herein.

FIELD OF THE INVENTION

The invention relates to implantable orthopaedic devices and may beparticularly relevant for spinal total disc replacement (TDR) implants.

BACKGROUND OF THE INVENTION

The vertebrate spine is made of bony structures called vertebral bodiesthat are separated by relatively soft tissue structures calledintervertebral discs. The intervertebral disc is commonly referred to asa spinal disc. The spinal disc primarily serves as a mechanical cushionbetween the vertebral bones, permitting controlled motions betweenvertebral segments of the axial skeleton. The disc acts as a joint andallows physiologic degrees of flexion, extension, lateral bending, andaxial rotation. To operate normally, the disc should have sufficientflexibility to allow these motions and have sufficient mechanicalproperties to resist the external forces and torsional moments caused bythe vertebral bones.

The normal disc is a mixed avascular structure having two vertebral endplates (“end plates”), an annulus fibrosis (“annulus”) and a nucleuspulposus (“nucleus”). Typically, about 30-50% of the cross sectionalarea of the disc corresponds to the nucleus. Generally described, theend plates are composed of thin cartilage overlying a thin layer ofhard, cortical bone that attaches to the spongy cancellous bone of thevertebral body. The end plates act to attach adjacent vertebrae to thedisc. Together, the annulus and nucleus support the spine by flexingwith forces produced by the adjacent vertebral bodies during bending,lifting, etc.

There are several types of treatment currently being used for treatingherniated or degenerated discs: conservative care, discectomy, nucleusreplacement, fusion and prosthesis total disc replacement (TDR). It isbelieved that many patients with lower back pain will get better withconservative treatment of bed rest. For others, more aggressivetreatments may be desirable.

Discectomy can provide good short-term results. However, a discectomy istypically not desirable from a long-term biomechanical point of view.Whenever the disc is herniated or removed by surgery, the disc spacewill narrow and may lose much of its normal stability. The disc heightloss may cause osteo-arthritis changes in the facet joints and/orcompression of nerve roots over time. The normal flexibility of thejoint is lost, creating higher stresses in adjacent discs. At times, itmay be necessary to restore normal disc height after the damaged dischas collapsed.

Fusion is a treatment by which two vertebral bodies are fixed to eachother by a scaffold. The scaffold may be a rigid piece of metal, oftenincluding screws and plates, or allo or auto grafts. Current treatmentis to maintain disc space by placement of rigid metal devices and bonechips that fuse two vertebral bodies. The devices are similar to mendingplates with screws to fix one vertebral body to another one.Alternatively, hollow metal cylinders filled with bone chips can beplaced in the intervertebral space to fuse the vertebral bodies together(e.g., LT-Cage™ from Sofamor-Danek or Lumbar I/F CAGE™ from DePuy).These devices have disadvantages to the patient in that the bones arefused into a rigid mass with limited, if any, flexible motion or shockabsorption that would normally occur with a natural spinal disc. Fusionmay generally eliminate symptoms of pain and stabilize the joint.However, because the fused segment is fixed, the range of motion andforces on the adjoining vertebral discs can be increased, possiblyenhancing their degenerative processes.

Some recent TDR devices have attempted to allow for motion between thevertebral bodies through articulating implants that allow some relativeslippage between parts (e.g., ProDisc®, Charite™), see, for example,U.S. Pat. Nos. 5,314,477; 4,759,766; 5,401,269 and 5,556,431. As analternative to the metallic-plate, multi-component TDR designs, aflexible solid elastomeric spinal disc implant that is configured tosimulate natural disc action (i.e., can provide shock absorption andelastic tensile and compressive deformation) is described in U.S. PatentApplication Publication No. 2005/0055099 to Ku, the contents of whichare hereby incorporated by reference as if recited in full herein.

Notwithstanding the above, there remains a need to provide alternativefixation structures that can help affix orthopaedic implants to localtissue or bone while also allowing for substantially normal disc action.

SUMMARY OF EMBODIMENTS OF THE INVENTION

Embodiments of the invention are directed to orthopaedic implants withselectively exposed mesh adapted for double integration fixation.

Molded orthopaedic implants include at least one mesh substrate havingopposing upper and lower primary surfaces. At least a major portion ofthe mesh substrate lower primary surface is integrally moldably attachedto the molded implant body. The mesh substrate has at least oneselectively exposed region devoid of molded material that exposes atleast a portion of the mesh substrate upper surface to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate.

The at least one exposed region can be a region that extends over atleast a major portion of the upper surface of the mesh substrate andthat extends into a partial thickness of the mesh substrate. The atleast one exposed region may have a gradient configuration wherebyincreasing amounts of molded material reside closer to the lower primarysurface.

The at least one exposed region can be a plurality of discrete spacedapart exposed regions that extend through the upper primary surface andextend a partial thickness into or wholly through the mesh substrate. Inparticular embodiments, some of the regions can be between about 5-10 mmin cross-sectional width.

In some embodiments, the implant can include an intermediate materiallayer residing between the lower primary surface of the mesh substrateand an upper portion of the molded body whereby the intermediatematerial layer resides proximate to the at least one exposed meshsubstrate region. The intermediate layer may be porous or non-porous(substantially impermeable) and may be formed of a single sheet ofmaterial or several discrete pieces.

Other embodiments are directed to methods of fabricating an implantableprosthesis. The methods include: (a) placing an inferior mesh layer on afloor of a three-dimensional mold; (b) introducing moldable materialinto the mold; (c) placing a superior mesh layer on a top surface of themoldable material in the mold; (d) heating the mold with the moldablematerial to a desired temperature so that the mold is heated; then (e)forming a molded implant body formed by the heated moldable materialwhereby the mesh layers are integrally moldably attached to the moldedbody formed by the moldable material; and (f) selectively exposing atleast one of the inferior and superior mesh layers so that at least oneregion is substantially devoid of the moldable material whereby theexposed region promotes tissue in-growth therein.

In some embodiments, the selectively exposing step includes placing atemporary mesh layer over at least a portion of at least one of an upperprimary surface of the superior layer or a lower primary surface of theinferior mesh layer, then after the forming step, removing the temporarymesh layer to selectively expose the mesh of the superior and/orinferior mesh layers while at least a major portion of the mesh layersare integrally molded to the molded implant body.

In some embodiments, the selectively exposing step comprises placingcalcium salt on selective regions of the inferior and superior meshlayers before the forming step.

In some embodiments, the selectively exposing step includes placing atemporary silicone layer over at least a portion of at least one of anupper primary surface of the superior layer or a lower primary surfaceof the inferior mesh layer to inhibit moldable material from entering atleast a top portion of the superior mesh layer or a bottom portion ofthe inferior mesh layer, respectively, during the forming step, thenafter the forming step, removing the temporary silicone layer toselectively expose the mesh of the superior and/or inferior mesh layers.

In some embodiments, the selectively exposing step includes placingintermediate mesh segment layers having smaller areas than the inferiorand superior mesh layers, between at least one of the superior layer orthe inferior mesh layer and the moldable material to locally inhibitmoldable material from entering selected regions of the superior meshlayer and the inferior mesh layer, respectively.

In some embodiments, the selectively exposing step includes placing anintermediate substantially impermeable layer between at least one of thesuperior layer or the inferior mesh layer and the moldable material tolocally inhibit moldable material from entering selected regions of thesuperior mesh layer or the inferior mesh layer, respectively, during theforming step.

In some embodiments, the selectively exposing step includes inhibitingthe moldable material from extending through localized regions of anupper portion of the superior mesh layer and a lower portion of theinferior mesh layer during the forming step.

In some embodiments, the selectively exposing step includes allowing themoldable material to enter the mesh superior and inferior layers whileinhibiting the moldable material from extending through at least a majorportion of an area of an upper portion of the superior mesh layer and alower portion of the inferior mesh layer during the forming step.

In some embodiments, the selectively exposing step includes flowing PVAhydrogel moldable material into the inferior and superior mesh layersduring the forming step whereby a density gradient of the hydrogelmoldable material extends in the mesh substrate whereby a lesser densityof moldable material resides on an outermost bounds of the implant body.

In some embodiments, the selectively exposing step comprises placing atemporary mesh layer comprising a resorbable material (e.g., anysuitable biocompatible salt) over at least a portion of at least one ofan upper primary surface of the superior layer or a lower primarysurface of the inferior mesh layer, then after the forming step,removing the temporary mesh layer to selectively expose the mesh of thesuperior and/or inferior mesh layers.

In some embodiments, the selectively exposing step comprises directingliquid, which may be pressurized to higher or lower pressures or evenunpressurized (just flowing), to remove molded material residing in atarget, localized region of at least one of the superior and inferiormesh layers.

Further features, advantages and details of the present invention willbe appreciated by those of ordinary skill in the art from a reading ofthe figures and the detailed description of the embodiments that follow,such description being merely illustrative of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a side perspective view of a spinal disc implant according toembodiments of the present invention.

FIG. 1B is a top view of a portion of the implant shown in FIG. 1A withan enlarged view of one region thereof.

FIG. 2A is a top view of a superior/inferior mesh layer that can be usedto form the implant shown in FIG. 1A according to embodiments of theinvention.

FIG. 2B is a top view of an annular mesh layer that can be used to formthe implant shown in FIG. 1A according to embodiments of the invention.

FIG. 3 is a front view of an implant similar to that shown in FIG. 1A inposition according to embodiments of the invention.

FIG. 4A is a schematic, exploded illustration of an implant with a meshlayer and a molded implant body according to embodiments of theinvention.

FIG. 4B is a schematic illustration of the implant shown in FIG. 4A withthe mesh substrate moldably attached thereto according to embodiments ofthe invention.

FIG. 4C is a schematic illustration of removable temporary layer(s) ofmaterial attached to the molded implant according to embodiments of thepresent invention.

FIG. 4D is a schematic illustration of the implant shown in FIG. 4Ahaving a naturally resorbable material according to embodiments of thepresent invention.

FIG. 5 is a schematic illustration of a different configuration of amesh layer with cooperating selective exposure material according toembodiments of the invention.

FIG. 6A illustrates an exploded view of an implant with the mesh layerand insert supplemental material used to form locally exposed regionsaccording to embodiments of the present invention.

FIG. 6B is a schematic illustration of the device shown in FIG. 6A withthe locally exposed mesh regions provided at demolding based on theinsert material according to embodiments of the present invention.

FIG. 6C is a top view of an alternate insert configuration that may beused in lieu of the insert shown in FIG. 6A according to embodiments ofthe present invention.

FIGS. 7A-7C are schematic illustrations of different configurations ofan implant with a mesh scaffold having removable material used to format least one exposed region (substantially devoid of hydrogel or othermoldable material) in the mesh layer according to embodiments of theinvention.

FIG. 8 is a schematic illustration of an implant with an inner layeraccording to embodiments of the invention.

FIG. 9A is a schematic illustration of an implant with the mesh layerhaving opposing upper and lower primary surfaces, at least a majorportion of the lower surface being integrally attached to the moldedbody such that the moldable material extends through a partial thicknessof the mesh substrate leaving an upper portion of the mesh substantiallydevoid of the molded material to facilitate tissue in-growth.

FIG. 9B is a schematic illustration of an implant with the mesh layerhaving opposing upper and lower primary surfaces, at least a majorportion of the lower surface being integrally attached to the moldedbody such that the exposed mesh extends through the mesh substrate tofacilitate tissue in-growth.

FIG. 10 is an exploded view of a mold with components used to make amolded primary implant body with a mesh scaffold and a removable outerlayer and/or an integrated internal shielding layer according toembodiments of the invention.

FIG. 11A is a schematic illustration of a pressurized fluid materialremoval system configured to remove local regions of molded (hydrogel)material from the mesh according to embodiments of the invention.

FIG. 11B is a schematic illustration of pressurized fluid system shownin FIG. 11A, with a template used to direct the fluid to targetlocations and/or shield non-target locations according to embodiments ofthe invention.

FIG. 12 is a schematic illustration of a mechanical material removalsystem according to embodiments of the invention.

FIG. 13 is a schematic illustration of a substantially encapsulatingshield cooperating with a solvent removal system according toembodiments of the present invention.

FIG. 14 is a schematic illustration of a pressurized material removalsystem with different exemplary exposed mesh configurations according toembodiments of the present invention.

FIG. 15 is a schematic illustration of a contacting pressurized removalsystem with an exemplary exposed mesh configuration according toembodiments of the invention.

FIG. 16 is a flow chart of operations that can be used to fabricatesurgical implants according to embodiments of the present invention.

DETAILED DESCRIPTION

The present invention now is described more fully hereinafter withreference to the accompanying drawings, in which embodiments of theinvention are shown. This invention may, however, be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein; rather, these embodiments are provided sothat this disclosure will be thorough and complete, and will fullyconvey the scope of the invention to those skilled in the art.

Like numbers refer to like elements throughout. In the figures, thethickness of certain lines, layers, components, elements or features maybe exaggerated for clarity. Broken lines illustrate optional features oroperations unless specified otherwise.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof. As used herein, the term “and/or”includes any and all combinations of one or more of the associatedlisted items. As used herein, phrases such as “between X and Y” and“between about X and Y” should be interpreted to include X and Y. Asused herein, phrases such as “between about X and Y” mean “between aboutX and about Y.” As used herein, phrases such as “from about X to Y” mean“from about X to about Y.”

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this invention belongs. It will befurther understood that terms, such as those defined in commonly useddictionaries, should be interpreted as having a meaning that isconsistent with their meaning in the context of the specification andrelevant art and should not be interpreted in an idealized or overlyformal sense unless expressly so defined herein. Well-known functions orconstructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being “on”,“attached” to, “connected” to, “coupled” with, “contacting”, etc.,another element, it can be directly on, attached to, connected to,coupled with or contacting the other element or intervening elements mayalso be present. In contrast, when an element is referred to as being,for example, “directly on”, “directly attached” to, “directly connected”to, “directly coupled” with or “directly contacting” another element,there are no intervening elements present. It will also be appreciatedby those of skill in the art that references to a structure or featurethat is disposed “adjacent” another feature may have portions thatoverlap or underlie the adjacent feature.

It will be understood that, although the terms first, second, etc. maybe used herein to describe various elements, components, regions, layersand/or sections, these elements, components, regions, layers and/orsections should not be limited by these terms. These terms are only usedto distinguish one element, component, region, layer or section fromanother region, layer or section. Thus, a first element, component,region, layer or section discussed below could be termed a secondelement, component, region, layer or section without departing from theteachings of the present invention. The sequence of operations (orsteps) is not limited to the order presented in the claims or figuresunless specifically indicated otherwise.

The terms “spinal disc implant” and “spinal disc prosthesis” are usedinterchangeably herein to designate total disc replacements using animplantable total spinal disc replacement prosthesis (rather than anucleus only) and as such are configured to replace the natural spinaldisc of a mammalian subject (for veterinary or medical (human)applications). In contrast, the term “spinal implant” refers to both TDRspinal disc implants and alternative spinal implants, such as, forexample, a spinal annulus or a spinal nucleus implant.

The term “flexible” means that the member can be flexed or bent. In someembodiments, the keel is flexible but has sufficient rigidity to besubstantially self-supporting so as to be able to substantially maintaina desired configuration outside of the body. The keel can includereinforcing materials and/or structure to increase its rigidity.

The term “keel” means an implant component, feature or member that isconfigured to be received in a recess or mortise in an adjacent bone tofacilitate short and/or long-term fixation and/or to provide twist ortorsion resistance in situ. The term “keel” also includes adiscontinuous keel configuration and/or a keel configuration that doesnot extend the entire length of the implant body, such as one or moreaxially aligned or offset keels.

The term “mesh” means any material in any form including, for example,knotted, braided, extruded, stamped, knitted, woven or otherwise, andmay include a material with a substantially regular foramination patternand/or an irregular foramination pattern.

The term “macropores” refers to apertures having at least about a 0.5 mmdiameter or width size, typically a diameter or width that is betweenabout 1 mm to about 3 mm, and more typically a diameter or width that isbetween about 1 mm to about 1.5 mm (the width dimension referring tonon-circular apertures). Where mesh keels are used, the macropores aretypically larger than the openings or foramina of the mesh substrate.The macropores may promote bony through-growth for increased fixationand/or stabilization over time.

The term “loop” refers to a shape in the affected material that has aclosed or nearly closed turn or configuration/shape. For example, theloop can have its uppermost portion merge into two contacting lowerportions or into two proximately spaced apart lower portions. The term“fold” means to bend over and the bend of the fold may have a sharp orrounded edge. The terms “pleat” or “fold” refer to doubling material onitself (with or without sharp edges).

The term “local” and derivatives thereof refers to target sub-portionsof the device rather than a global feature. The term “orthopaedic”refers to medical implants or devices used to treat disorders of theskeletal system and related motor organs.

The term “film” refers to a thin material, typically between about 0.001mm to about 0.5 mm thick, and may be porous or non-porous (e.g.,substantially or totally impermeable).

As shown in FIGS. 1A and 1B, an implant 10 can include at least oneporous mesh material layer 10 m, shown as including three discretelayers 11, 12, 13 that can be moldably attached to a primary molded body10 b. In the embodiment shown, the mesh layers 10 m include superior andinferior primary surface mesh-covering layers 11, 13, respectively andan annulus surface mesh-covering layer 12. The annulus layer 12 can beformed as a continuous or seamed ring to radial and/or axial expansionof the body 10 b. In other embodiments, the annulus cover layer 12 canbe discontinuous about the molded primary body 10 b.

As shown, the implant 10 may also include at least one flexible keel 15on each of the end plate surfaces formed by the mesh material 11, 13.FIG. 3 illustrates that the keel 15 can reside in a mortise in adjacentbone when implanted. One or more pre-molding apertures and/orpost-molding apertures (macropores) may be formed in the keel 15 and/orskirt 14 for vertebral bone attachment. If a cutting process is used,the cutting process (e.g., ultrasonic cutting, laser cutting, thermalcutting, RF cutting or other suitable techniques) may locally melt thetwo layers of mesh or keel pieces together, creating at that point afused direct connection between the two layers.

FIG. 3 also illustrates a different shape of the skirt 14. Although theimplant 10 is shown as a spinal (TDR) disc shape and is primarilydescribed with respect to this embodiment for clarity of discussion, theimplant 10 can have other shapes according to a desired function andtarget repair site, and is not limited to spinal disc implants.

The molded body 10 b can be of any suitable biocompatible materialappropriate to the target repair site, typically an elastomericmaterial, such as polymer, co-polymer or derivatives or combinationsthereof. In particular embodiments, the implant 10 can be a TDR implantthat has a solid unitary body 10 b of molded crystalline hydrogel ofpolyvinyl alcohol (PVA) known as Salubria® from SaluMedica, Inc.,located in Atlanta Ga.

Similarly, the mesh 10 m can be of any suitable biocompatible material.Where mesh layers 10 m are used on more than one surface, the differentmesh layers may be of different mesh material, thickness and/or meshporosity. As shown, in FIGS. 1A and 1B, the endplate mesh layers 11, 13may have a different mesh pattern than the mesh ring 12, with theperipheral mesh ring 12 having smaller pore sizes from that of theendplate mesh layers 11, 13. The pore dimensions of thesuperior/inferior (e.g., endplate) mesh layers 11, 13 can be selected topromote tissue in-growth. Exemplary pore sizes for tissue ingrowthand/or bone ingrowth into the exposed mesh scaffold of the endplate meshlayers 11, 13 is typically between about 0.5 mm to about 1 mm. Smallerpore sizes may be used on the annular mesh layer 12, typically betweenabout 0.1 mm to about 0.5 mm as this mesh 12 may not be exposed (e.g.,is substantially encapsulated in the mold material) and has a desiredstrength related to mesh density. The mesh layers 11, 13 can be anysuitable thickness and pore pattern configured to promote tissuein-growth, and may typically be between about 0.5 mm to about 5 mmthick, more typically between about 0.7 mm to about 2 mm thick, such asabout 0.75 mm thick.

In some embodiments, the mesh layers 10 m can all be polyester meshlayers that may be extruded, knitted, braided, woven or otherwise formedinto a mesh pattern. In some embodiments, the mesh comprises amulti-filament fiber(s) that can provide increased strength overconventional polyester material. For example, the mesh 10 m can compriseyarns of a polyester mesh multifilament fiber that, for example, can bemade out of a High Tenacity Polyester Teraphthalate (HTPET), whichtypically has a longer molecular chain than conventional polyestermaterial, therefore providing more strength to the mesh than a regularpolyester material. In some embodiments, the mesh can be a high strengthmesh that using a ball burst test (ref. ASTM D3787-01), can have a burstvalue between about 1500-3000N and also a slope of the linear portion ofthe load/displacement curve of between about 150-300 N/mm. In particularembodiments, one or more of the mesh layers 11, 12, 13 can include ahigh strength polyester mesh of about 0.7 mm thick that is similar to orthe same as that available as Fablok Mills Mesh #9464 from Fablok Mills,Inc., located in Murray Hill, N.J.

As shown in FIGS. 1A, 1B, 2A, and 2B, the TDR implant 10 includes threeseparate pieces of mesh covering material 11, 12, 13 that are eachintegrally molded to attach to the primary body 10 b of the implant; oneto the upper primary surface; one to the lower primary surface; and oneas a peripheral ring around the outer upwardly extending surface. Theupper and lower primary surfaces are also known as endplate surfaces. Asshown in FIG. 1B, the edges of the three pieces of mesh are not requiredto attach together but can be each integrally molded to the implantbody, embedded, at least partially, in the moldable (e.g., PVA)material. One purpose of the endplate mesh 11, 13 can be to promotetissue in-growth. The peripheral mesh ring 12 can embed in the molded(e.g., PVA) material so as to increase radial strength of the implant tolimit radial expansion under load, but the mesh ring 12 may besufficiently covered and/or embedded in the molded body so as to inhibittissue in-growth therein.

FIGS. 2A and 2B illustrate exemplary configurations of the differentmesh pieces 11, 12, 13. FIG. 2B illustrates the peripheral (annulus)mesh ring 12 and FIG. 2A illustrates examples the top and bottom endplate mesh pieces 11, 13. The top and bottom end plate pieces 11, 13 aretypically the same or substantially similar, the endplate geometry mayvary slightly due to different convexivity of the endplates. As shown,the ends 12 e of the peripheral mesh ring can be detached until moldedto the implant body as an outer ring. However, in an alternative design,the peripheral mesh ring is a continuous tube or ring member. The ringwith the molded polymer body 10 b can limit radial expansion of the body10 b in situ. The flexibility of the molded body 10 b and integrallyattached peripheral mesh ring 12 may allow some limited radialexpansion.

As shown in FIGS. 1A, 1B, 2A and 2B, the implant 10 can use acontinuation or extension of each of the three pieces of mesh material11 s, 12 s, 13 s to form a skirt 14 (which can also be described as atab) reinforced with the molded material, to provide a means forattaching to vertebral bodies. In particular embodiments, the skirt 14can be between about 1-4 mm thick, typically about 2 mm thick. For thelatter, each of the mesh layers can be about 0.75 mm thick. Theadditional thickness of the skirt 14 is due to the mold material thatcovers and embeds the layers forming the skirt material 14. None of themesh layers are required to extend over edges or corners and the mesh isnot required to encapsulate the molded body.

The endplate mesh layers 11, 13 may restrain the expansion of the body10 b to some extent in the radial direction, but typically not in theaxial direction. The peripheral mesh ring 12 may slightly restrain theprimary molded body 10 b (e.g., PVA core) in the axial direction due tohydration and the peripheral mesh ring will also limit radial expansionas discussed above. The implant 10 may have certain swelling propertiesand may be able to expand in all directions between about 1-5% betweendemolding and full hydration and while unloaded. Also, the implant 10can be configured to regain height by rehydration when unloaded afterheight loss due to compressive force. The device 10 may not gain heightin situ if unloaded if it does not lose height in the first place.

One primary purpose of the peripheral mesh ring 12 can be to increaseradial strength to limit radial expansion under load. The mesh ring 12may be embedded in the molded material to a sufficient degree so that itdoes not promote or have significant tissue in-growth. In addition, thetissue in-growth is inhibited if the mesh is not exposed or if the poresize is too small. For example, an exposed peripheral mesh layer havinga very small pore size may not experience in-growth.

As noted above, one primary purpose of the mesh on the endplates 11, 13can be to promote attachment of the device's endplate to the vertebralbodies, primarily by tissue in-growth. To that end, the mesh on at leastone of the endplates 11, 13 can be processed before, during and/or aftermolding to locally expose mesh that otherwise would be or is coveredwith molded material (e.g., hydrogel) in order to promote the tissuein-growth. The exposure can be carried out so that the mesh isconfigured to allow for double integration of mesh for fixation oforthopaedic devices: on the one hand, fixation with the device's mainmaterial (in some embodiments, hydrogel) and on the other hand, fixationwith human tissues (fibrous and/or bone, depending on location and useof the implanted device).

FIG. 4A illustrates that at least one “temporary” removable, solvableand/or resorbable material 20 can be placed over or under the mesh 10 mbefore the mesh 10 m is moldably attached to the implant body 10 b(while the moldable material is viscous). Where the temporary material20 is to be implanted, it may comprise a bone substitute. If it isremoved prior to implantation it may comprise any suitable material suchas any kind of salt, including, for example, calcium salt.

FIG. 4B illustrates the mesh 10 m being moldably attached to the body 10b with the removable, solvable or resorbable material remainssubstantially in position in/on the mesh 10 m. FIG. 4C illustrates thatthe material 20 can be removed to show the locally exposed regions 10 eof the mesh 10 m. In some embodiments, the material 20 can be peelablyremoved as shown in FIG. 4C. The material can be a temporary“shield-like” material that is substantially non-porous or less porousthan the mesh 10 m. For example, the material 20 can be an elastomericor metal material (or combinations of same, such as an elastomeric sheetor layer with metallic foil backing), such as an impermeableheat-resistant film or conformable flexible metal, either of which maybe configured as a single larger piece with apertures or smaller pieces,or other polymer layer configurations, e.g., dollops of silicone, one ormore pieces of a second, denser mesh layer, and the like.

In some embodiments, the material 20 can include a material that issolubilized or resorbed to form the locally exposed region(s) 10 e. Forexample, the material 20 can include calcium salt, hydroxyapatite,calcium phosphates and/or any other resorbable and/or solubilizablematerial to temporarily fill a target volume/area of mesh 10 m to expose(e.g., inhibit mold material from integrating thereat). Differentmaterials 20 with different resorbtion rates may be used, typicallytaking between 3 weeks to several years to substantially resorb afterimplantation.

The exposed region 10 e can extend over substantially an entire or wholeprimary surface, through partial thickness of the mesh 10 m, or theexposed region 10 e can be local—one or several sub-portions ofsegments. For the latter, the exposure can be through a partialthickness for each or some local regions 10 e, or throughout the wholethickness of the mesh at that region(s), which may provide improvedtissue bonding.

In some embodiments, the material 20 can comprise a viscous liquid suchas silicone that can be injected, poured or otherwise provided on theprimary surface of the mesh 10 m, then cured or otherwise treated tosolidify the material.

After the molding process, which integrates the mesh 10 m to the implantbody 10 b, the temporary material 20 can be chemically, electrically,optically or mechanically removed. For example, the temporary material20 can also be removed during manufacturing using solvent and/ormechanical removal, such as, but not limited to, vibration, peeling ofmaterial, brushing of the material, evacuation of the material and thelike. In some embodiments, where a viscous liquid is used, the viscousliquid can be solidified, then peeled-off of the surface of the mesh 10m to provide the region(s) 10 c. With viscous liquids such as silicone,it is contemplated that the size of the mesh pores to be exposed can begenerally or substantially controlled by selecting an appropriateviscosity or durometer, whereby a lower viscosity or durometer canoccupy larger areas and/or fill smaller pores to migrate further(deeper) into the mesh layer 10 m.

In some embodiments, the material 20 can be a “mesh peel layer” where asection of mesh, impregnated with CaS or other anti-stick materialsuitable to facilitate removal after exposure to the molding process,can be placed on and/or a depth into the uppermost (or lowermost)primary surface of the target mesh 10 m (i.e., inferior and superiorendplates 11, 13) through the molding process, then peeled, pulled orscraped off at demolding.

In some embodiments, all or some of the material 20 remains in place atimplantation, and, if bio-resorbable, the tissue ingrowth can occurwhile the material 20 is resorbed (e.g., calcium salt). This techniquemay inhibit collapse of the exposed mesh scaffold 10 e under compressiveloads.

FIG. 5 illustrates that an insert material 30 can be placed between themesh 10 m and the primary implant molded body 10 b. The insert material30 may be used alone (FIG. 6A) or with the temporary outer material 20(FIG. 5). The insert material 30 can be configured to locally inhibitthe moldable material (e.g., hydrogel material) from flowing out throughthe mesh 10 m during molding. The flowing of the moldable materialthrough the mesh 10 m typically allows the mold material to enter andembed the mesh 10 m to attach the mesh to the implant body 10 b. Asshown in FIG. 6B, by locally inhibiting this interaction during molding,the material 30 can provide an exposed region 10 e at the point ofdemolding of the formed device, without requiring additional processing.The insert material 30 can be configured as small insert sections 30 sof high density/low porosity mesh which can be located adjacent to andright underneath the mesh 10 m (e.g., the endplate mesh layers 11, 12).Those allow the irrigation fluid (e.g., saline) but not the liquid(molten) mold material (e.g., hydrogel) to flow through. Alternatively,or additionally, small sections of film 30 s (substantiallyimpermeable/or without porosity) can be used as the inner material 30.The film can comprise an elastomer, such as a polymer, copolymer orderivatives thereof, such as silicone, TEDLAR and other suitableheat-resistant materials. Again, during molding, the irrigant (e.g.,saline) can flow around the insert, but not the moldable material (e.g.,hydrogel) that forms the primary body 10 b and integrates into the otherportions of the mesh 10 m. At demolding, the saline in thenon-integrated mesh regions flows out/dehydrated, leaving an exposedarea 10 c of mesh.

Where small pieces of insert material 30 are used, the small sectionsmay have an area of between about 1 mm² to about 25 mm². The inserts 30can be provided as combinations of different material types, such aspieces of mesh and film.

Alternatively, as shown in FIG. 6C, the film, mesh or other insertmaterial 30 can be configured as a single layer with a pattern ofapertures 30 p to allow sufficient transfer of irrigant to permit atleast a major portion of the mesh 10 m to moldably affix to the implantbody 10 b while also providing exposed mesh 10 e. A similar shieldtemporary layer 20 may also be used in lieu of smaller droplets,globules or pieces of material 20.

FIGS. 7A-7C illustrate different exposed mesh regions 10 e that can beformed using removable material 20 according to embodiments of thepresent invention. The mesh 10 m (e.g., mesh scaffold) is moldablyattached to the primary implant body 10 b typically formed of a solidfreeze-thaw crystalline hydrogel. The moldable material 100 isconfigured to flow through the mesh during the molding process tointegrate into the mesh 10 m. The removable material 20 is configured toexpose certain portions of the mesh to allow tissue in-growth. FIG. 7Aillustrates that the material 20 can be configured to cover a relativelylarge region of the mesh 10 m from a first primary surface to a partialdepth or thickness t_(p). FIG. 7B illustrates that the material 20 canbe configured to reside locally at a relatively small segment of themesh and extend through the mesh 10 m substantially to a total or wholethickness, t_(w). FIG. 7C illustrates that the material 20 can extend toseveral depths or thickness, including partial (which extends over agreater surface area), and through the mesh entirely to a depth of t_(t)to contact an upper (or lower) portion of the molded body 10 b. Theremovable material 20 can be removed to define the locally exposedregions 10 e of the mesh 10 m.

FIG. 8 illustrates an exemplary use of the insert material 30. As shown,the insert member 30 resides under the mesh 10 m (mesh scaffold)adjacent a top portion of the molded implant body 10 b. Duringprocessing, the moldable material 100 may flow over the edges of theprotective insert material 30. Typically, a gradient of moldablematerial will be formed between the liquid irrigant (water or saline)volume 200 and the moldable material volume (forming the primary implantbody 10 b), lesser to greater. The liquid 200 can be removed afterprocessing to provide the exposed mesh 10 e.

FIG. 9A illustrates an implant 10 with an integrated mesh 10 m such thatat least a major portion of the contact surface 10 c of the mesh 10 m ismoldably attached to the implant body 10 b and the mesh 10 m has atleast one locally exposed region 10 e that extends a partial depththickness t_(p) of the mesh 10 m. The region 10 e may be relativelylarge and contiguous or discontinuous and may occupy between about20-70% of the upper surface and extend to a partial depth over most ofthat region, with potentially deeper depth extension in sub-regions. Asshown in FIG. 9B, where smaller localized regions 10 c are used, theregions 10 e may extend partially, but typically at least some regions10 e extend through or to a total mesh depth t_(w). Where a keel 15(FIG. 1A) is used, the regions 10 e can be configured to accommodatethis feature.

FIG. 10 is an exploded view of a mold 210 with components used to make amolded primary implant body 10 b with two mesh scaffolds 10 m and aremovable outer material 20 and/or an integrated internal insertmaterial 30 used to form the exposed region(s) according to embodimentsof the invention. As shown the lower mesh 10 m can be placed in the mold210 and the moldable material can be placed over the lower mesh 10 m.The upper mesh 10 m can be placed on top of the moldable material 200.Liquid irrigant 200 can be added before and/or after the lid 212 isplaced on the mold 210. The lid 210 can have a channel or port to addliquid 200. The insert material 30 and/or the removable material 20 canbe placed in the order needed to have them in the mold and incommunication with the respective mesh 10 m at the appropriate time.That is, for the insert 30, the insert material can be placed after thelower mesh 10 m is placed in the mold 210, before the moldable material100 is added. In contrast, where a removable material 20 is used, thematerial 20 can be placed on the lower part (outer surface) of the mesh10 m and/or in the bottom of the mold prior to placing the mesh in themold. For the top mesh 10 m, where an insert material 30 is used, thematerial 30 can be placed on the moldable material 100 or on theunderside of the mesh 10 m before the mesh is added to the mold 210. Forthe removable material 20, the material can be added to the mesh 10 mbefore, during or after the mesh 10 m is placed in the mold. The lid 212can enclose the components therein and the mold can be placed at thedesired temperature to mold the body and attach the mesh thereto. Theexposed regions 10 e may exist at demolding, or may be exposed afteradditional processing.

Alternatively, the exposed regions 10 e can be formed after demoldingwithout the use of either material 20 or 30, using chemical, optical,mechanical or electrical formation means. Combinations of any of theabove may also be used.

FIG. 16 illustrates exemplary operations that can be used to form atleast one exposed mesh region in a molded implant with inferior andsuperior mesh layers. As shown, an inferior mesh layer can be placed ona floor of a three-dimensional mold (block 400). Moldable material canbe introduced into the mold (block 410). A superior mesh layer can beplaced over the moldable material (block 420). The mold with themoldable material and mesh can be heated (block 430). The molded implantbody is formed by the heated molded material whereby the mesh layers areintegrally molded to the implant body formed by the molded material(block 440). At least one of the inferior and superior mesh layers isselectively exposed so that at least one region thereof is devoid ofmoldable material whereby the exposed region allows for tissue in-growthin situ (block 450).

As shown in FIG. 11A, a fluid removal system 300 using pressurized fluid300 f delivered via one or more flow jets or nozzles 300 n can be usedto form locally exposed regions 10 e in the mesh 10 m. No specialpreparation is required to form the exposed mesh before molding. Rather,after demolding, the molded material (e.g., hydrogel) can be“pressure-washed” or removed from the desired local area/volume of meshusing a pressurized fluid, typically a heated sterile liquid at atemperature between about 70° C.-95° C., such as heated sterile water orsaline.

In some embodiments, a focal water jet (pressurized to between about 50psi to about 150 psi) can be pulsed at a desired frequency, typicallybelow about 100 Hz, such as at about 50 Hz to about 5 Hz, typicallyabout 20 Hz, to improve removal of the molded material 100. This processcan be carried out to remove material in depth (throughout the layer ofmesh and even below).

FIG. 11B illustrates a mask 300 m with apertures can be used to helpdirect the fluid to form the desired exposed regions 10 e and/or helpshield non-target mesh regions. The fluid may be a sterile liquid, suchas heated saline or water.

FIG. 12 illustrates that a stiff brush 325, such as a wire brush, can beused to contact the molded body and mesh 10 m to remove molded material100 to expose local regions of mesh. The brush 325 or other mechanicaldevice can be used with moisture (solvent) and/or heat to facilitate theremoval.

FIG. 13 illustrates that the molded implant 10 with integrated mesh 10 mcan be substantially encapsulated in a shield 400 with locally exposedregions 400 e. This encapsulated body 400 b can open only the targetarea(s) to expose those areas where the molded material is desired to beremoved. The encapsulated body 400 b can then be immersed in a bath 402of solvent, which would substantially contact only the area(s) toexpose. The bath 402 can comprise heated liquid, such as sterile(sub)boiling water. The bath 402 may be stationary or may vibrate and/oroscillate similar to a dishwasher. This method emphasizes thenon-directional use of the solvent.

FIG. 14 illustrates another fluid removal system 300. In thisembodiment, the system 300 includes a controlled-temperature liquidreservoir 310, a pump 305, a nozzle 300 n and an overflow or liquidcapture container 320. If the used liquid is re-used in a re-circulatingcontained circuit, a filter 311 can be placed between the reservoir 310and the container 320. If the waste or used liquid is disposed, then thefilter may not be required. The pressurized fluid 300 f employed in thecontained circuit to remove the material 100 can be pressurized hotwater. The system 300 can form exposed regions 10 e with eitherpartially, totally or even deeper exposure regions as shown by theexemplary exposed region 10 e configurations to the right of the system300 in FIG. 14.

FIG. 15 illustrates a fluid removal system 300 with a fixture 325 with achamber 327 that is in communication with inlet and exit flow paths 330i, 330 e and abuts a primary surface of the mesh 10 m. The controlledtemperature reservoir 310 can connect to the chamber 327 with a pipediameter of about 2 mm. The chamber 327 can have about a 5 mm diameter(or width) and about a 5 mm height (“h”) (corresponding to the area ordiameter of the target region to expose) with between about a 90 degreeto about a 180 degree angle between the input 330 i and output 330 e.The diameter change and angles create a pressure drop and a turbulentflow around the molded material 100 (e.g., hydrogel) to facilitatematerial removal. The chamber-based system and/or method providescontrol of depth of exposed region of mesh as the solvent flowssubstantially tangentially to the mesh, which eventually dampens/shieldsthe internal core material (e.g., the primary implant body 10 b). Thus,FIGS. 14 and 15 illustrate that in some embodiments, the selectivelyexposing step comprises directing liquid, which may be pressurized tohigher or lower pressures, or even unpressurized (just flowing), toremove molded material residing in a target, localized region of atleast one of the superior and inferior mesh layers.

For each of the fluid removal systems, the pump 305 used can be anysuitable pump, such as, but not limited to, a peristaltic pump, and mayprovide a typical flow rate of between about 250-1000 mL/min.

As noted above, a chemical removal/breakdown of the molded material 100(e.g., hydrogel) can also or alternatively be used to remove the moldedmaterial from a desired area/volume of mesh 10 m. Also, any combinationor two or more of the above methods can be used. For example, using theinsert 30 or shield layer 20 to selectively expose the mesh duringmolding, then washing such as using the pressurized fluid may remove anyresidual mold material such as, for example, low weight % hydrogel.

In some embodiments, the shape of the implant 10 can be described as athree-dimensional structure that provides anatomical shape, shockabsorbency and mechanical support. The anatomical shape can have anirregular solid volume to fill the target intervertebral disc space. Thecoordinates of the body can be described using the anatomic directionsof superior (towards the head), inferior (towards the feet), lateral(towards the side), medial (towards the midline), posterior (towards theback), and anterior (towards the front). From a superior view, theimplanted device has a kidney shape with the hilum towards the posteriordirection. The margins of the device in sagittal section are generallycontained within the vertebral column dimensions. The term “primarysurface” refers to one of the superior or inferior surfaces.

The molded implant 10 can be made from any suitable elastomer capable ofproviding the desired shape, elasticity, biocompatibility, and strengthparameters. The implant 10 can be configured with a single, uniformaverage durometer material and/or may have non-linear elasticity (i.e.,it is not constant). The implant 10 may optionally be configured with aplurality of durometers, such as a dual durometer implant. The implant10 can be configured to be stiffer in the middle, or stiffer on theoutside perimeter. In some embodiments, the implant 10 can be configuredto have a continuous stiffness change, instead of two distinctdurometers. A lower durometer corresponds to a lower stiffness than thehigher durometer area. For example, one region may have a compressivemodulus that is between about 11-100 MPa while the other region may havea compressive modulus that is between 1-10 MPa.

The implant 10 can have a tangent modulus of elasticity that is about1-10 MPa, typically about 3-5 MPa, and water content of between about30-60%, typically about 50%.

Some embodiments of the implantable spinal disc 10 can comprisepolyurethane, silicone, hydrogels, collagens, hyalurons, proteins andother synthetic polymers that are configured to have a desired range ofelastomeric mechanical properties, such as a suitable compressiveelastic stiffness and/or elastic modulus. Polymers such as silicone andpolyurethane are generally known to have (compressive strength) elasticmodulus values of less than 100 MPa. Hydrogels and collagens can also bemade with compressive elasticity values less than 20 MPa and greaterthan 1.0 MPa. Silicone, polyurethane and some cryogels typically haveultimate tensile strength greater than 100 or 200 kilopascals. Materialsof this type can typically withstand torsions greater than 0.01 N-mwithout failing.

Although shown as substantially conformally covering substantially theentire respective surfaces of the implant, one or more of the layers 11,12, and 13 may occupy a smaller portion of the respective surface (notshown).

Some embodiments of the spinal disc implant 10 are configured so thatthey can mechanically function as a substantially normal (natural)spinal disc and can attach to endplates of the adjacent vertebralbodies. The implant 10 can expand in situ to restore the normal heightof the intervertebral space. The implant 10 can be configured to expand,for example, between about 1-40%, typically about 1-5%, afterimplantation relative to its configuration at the time of implantation.It is envisioned that the spinal disc implant 10 can be inserted by asurgical procedure into the target intervertebral space. It may be usedfor separation of two bony surfaces within the spine. In otherembodiments, the implant may be configured for use with respect to otherbones of the body.

As shown in FIG. 1A, the spinal disc body 10 is generally of kidneyshape when observed from the superior, or top, view, having an extendedoval surface and an indented portion. The implant 10 can be configuredwith a mechanical compressive modulus of elasticity of about 1.0 MPa,ultimate stretch of greater than 15%, and ultimate strength of about 5MPa. The device can support over 1200 N of force. Further description ofan exemplary flexible implant is described in co-pending U.S. PatentApplication Publication No. 20050055099, the contents of which arehereby incorporated by reference as if recited in full herein.

Elastomers useful in the practice of the invention include siliconerubber, polyurethane, polyvinyl alcohol (PVA) hydrogels, polyvinylpyrrolidone, poly HEMA, HYPAN™ and Salubria® biomaterial. Methods forpreparation of these polymers and copolymers are well known to the art.Examples of known processes for fabricating elastomeric cryogel materialare described in U.S. Pat. Nos. 5,981,826 and 6,231,605, and co-pending,co-assigned U.S. Patent Application Ser. No. 60/60/761,902, the contentsof which are hereby incorporated by reference. See also, Peppas, Poly(vinyl alcohol) hydrogels prepared by freezing—thawing cyclicprocessing. Polymer, v. 33, pp. 3932-3936 (1992); Shauna R. Stauffer andNikolaos A. Peppas.

The moldable material comprises an irrigant and/or solvent and cancomprise between about 25 to 60% (by weight) PVA powder crystals. ThePVA powder crystals can have a MW of between about 124,000 to about165,000, with about a 99.3-100% hydrolysis. The irrigant or solvent canbe a solution of about 0.9% sodium chloride. The PVA crystals can beplaced in the mold 210 (FIG. 10) before the irrigant (no pre-mixing isrequired). The lid 212 can be used to close the mold 210. The closedmold 200 can be evacuated or otherwise processed to remove air bubblesfrom the interior cavity. For example, the irrigant can be overfilledsuch that when the lid is placed on (clamped or secured to) the mold210; the excess liquid is forced out thereby removing air bubbles. Inother embodiments, a vacuum can be in fluid communication with the moldcavity to lower the pressure in the chamber and remove the air bubbles.The PVA crystals and irrigant can be mixed once in the mold or beforeand placed in the mold together and/or some or all of the irrigant canbe introduced after the lid is closed. Alternatively, the mixing canoccur naturally without active mechanical action during the heatingprocess. The irrigant or solvent can comprise saline which may beprovided as a solution of about 0.9% sodium chloride. The PVA crystalscan be placed (dry) in the mold independently of, typically before, theirrigant (no pre-mixing is required) and/or otherwise introduced intothe mold so that injection is not required. The irrigant and PVA, orjust the irrigant, can be inserted into a mold after a lid is attachedusing a liquid vent port that can be plugged or sealed before thematerial and the mold are heated. After cooling, the hydrogel-moldedbody can be further processed without placing in water or saline duringsubsequent processing. The hydrogel body can be hydrated at leastpartially before packaging and/or before implantation.

Typically, for PVA mold material, the mold 210 with the moldablematerial is heated to a temperature of between about 80° C. to about200° C. for a time sufficient to form a solid molded body. Thetemperature of the mold can be measured on an external surface. The moldcan be heated to at least about 80-200° C. for at least about 5 minutesand less than about 8 hours, typically between about 10 minutes to about4 hours, the (average or max and min) temperature can be measured inseveral external mold locations. The mold can also be placed in an ovenand held in the oven for a desired time at a temperature sufficient tobring the mold and the moldable material to suitable temperatures. Insome embodiments, the mold(s) can be held in an oven at about 100-200°C. for about 2-6 hours. The higher range may be used when several moldsare placed therein, but different times and temperatures may be useddepending on the heat source, such as the oven, the oven temperature,the configuration of the mold, and the number of items being heated.

For PVA mold material, after heating, the implant body 10 b can becooled passively or actively and/or frozen and thawed a plurality oftimes until a solid crystalline implant is formed with the desiredmechanical properties. The molded implant body can be removed from themold prior to the freezing and thawing or the freezing and thawing canbe carried out with the implant in the mold. Alternatively, some of thefreeze and thaw steps (such as, but not limited to, between about 0-10cycles) can be carried out while the implant is in the mold, then others(such as, but not limited to, between about 5-20 cycles) can be carriedout with the implant out of the mold.

Before, during and/or after freezing and thawing (but typically afterdemolding), the molded implant 10 can be placed in water or saline (orboth or, in some embodiments, neither). The device 10 can be partiallyor completely dehydrated for implantation. The resulting prosthesis canhave an elastic modulus of at least about 2 MPa and a mechanicalultimate strength in tension and compression of at least 1 MPa,preferably about 10 MPa, and under about 100 MPa. The prosthesis mayallow for between about 1-10 degrees of rotation between the top andbottom faces with torsions of at least about 1 N-m without failing. Theimplant can be a single solid elastomeric material that is biocompatibleby cytotoxicity and sensitivity testing specified by ISO (ISO 10993-51999: Biological evaluation of medical devices—Part 5: Tests for invitro cytotoxicity and ISO 10993-10 2002: Biological Evaluation ofmedical devices-Part 10: Tests for irritation and delayed-typehypersensitivity.).

The testing parameters used to evaluate the compressive tangentialmodulus of a material specimen can include:

Test type: unconfined compression Fixtures: flat platens, at least 30 mmdiameter Rate: 25.4 mm/sec to 40% strain Temperature: room temp (~22°C.) Bath: samples stored in saline or water until immediately beforetest Samples: cylinders, 9.8 ± 0.1 mm height, 9.05 ± 0.03 mm diameterCompressive Tangential Modulus calculated at 15, 20, and 35% strain

Because the implants can be manufactured to be mechanically strong, orto possess various levels of strength among other physical properties,the process can be adapted for use in many applications. Cryogel-basedmold material also has a high water content, which provides desirableproperties in numerous applications. For example, the cryogel tissuereplacement construct is especially useful in surgical and other medicalapplications as an artificial material for orthopedic implants in humansand other mammals.

Orthopaedic implants include, but are not limited to, back, knee, armimplants, hip and knee joint replacements, load bearing surface implantsand prosthetic limbs.

The foregoing is illustrative of the present invention and is not to beconstrued as limiting thereof. Although a few exemplary embodiments ofthis invention have been described, those skilled in the art willreadily appreciate that many modifications are possible in the exemplaryembodiments without materially departing from the novel teachings andadvantages of this invention. Accordingly, all such modifications areintended to be included within the scope of this invention as defined inthe claims. The invention is defined by the following claims, withequivalents of the claims to be included therein.

1. A molded orthopaedic implant comprising at least one mesh substratehaving a thickness of between about 0.5 mm to about 5 mm, havingopposing upper and lower primary surfaces, wherein at least a majorportion of the mesh substrate lower primary surface is integrallymoldably attached to a molded primary implant body, wherein the meshsubstrate has at least one selectively exposed region devoid of moldedmaterial associated with the molded primary implant body that exposes aportion of an outermost surface of the mesh substrate to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate, andwherein the at least one mesh substrate outermost surface has regionsthat include the molded material associated with the primary implantbody, wherein the at least one exposed region is a plurality of discretespaced apart exposed regions that extend through the upper primarysurface and extend a partial thickness into the mesh substrate.
 2. Amolded orthopaedic implant comprising at least one mesh substrate havinga thickness of between about 0.5 mm to about 5 mm, having opposing upperand lower primary surfaces, wherein at least a major portion of the meshsubstrate lower primary surface is integrally moldably attached to amolded primary implant body, wherein the mesh substrate has at least oneselectively exposed region devoid of molded material associated with themolded primary implant body that exposes a portion of an outermostsurface of the mesh substrate to at least a partial thickness of themesh substrate so as to allow for tissue in-growth in the at least oneexposed region of the mesh substrate, and wherein the at least one meshsubstrate outermost surface has regions that include the molded materialassociated with the primary implant body, wherein the at least oneexposed region is a plurality of discrete spaced apart exposed regionsextending wholly through the mesh substrate.
 3. A molded orthopaedicimplant comprising at least one mesh substrate having a thickness ofbetween about 0.5 mm to about 5 mm, having opposing upper and lowerprimary surfaces, wherein at least a major portion of the mesh substratelower primary surface is integrally moldably attached to a moldedprimary implant body, wherein the mesh substrate has at least oneselectively exposed region devoid of molded material associated with themolded primary implant body that exposes a portion of an outermostsurface of the mesh substrate to at least a partial thickness of themesh substrate so as to allow for tissue in-growth in the at least oneexposed region of the mesh substrate, and wherein the at least one meshsubstrate outermost surface has regions that include the molded materialassociated with the primary implant body, and further comprising anintermediate material layer residing between the lower primary surfaceof the mesh substrate and an upper portion of the molded body wherebythe intermediate material layer resides proximate to the at least oneexposed mesh substrate region, wherein the mesh substrate is an outermesh substrate adapted to contact local tissue when implanted, andwherein the intermediate layer comprises a second inner mesh substratewith a smaller pore size than the outer mesh substrate and that is sizedand configured in small sections that cooperate with the outer meshsubstrate to define the at least one exposed region.
 4. A moldedorthopaedic implant comprising at least one mesh substrate having athickness of between about 0.5 mm to about 5 mm, having opposing upperand lower primary surfaces, wherein at least a major portion of the meshsubstrate lower primary surface is integrally moldably attached to amolded primary implant body, wherein the mesh substrate has at least oneselectively exposed region devoid of molded material associated with themolded primary implant body that exposes a portion of an outermostsurface of the mesh substrate to at least a partial thickness of themesh substrate so as to allow for tissue in-growth in the at least oneexposed region of the mesh substrate, and wherein the at least one meshsubstrate outermost surface has regions that include the molded materialassociated with the primary implant body, and further comprising anintermediate material layer residing between the lower primary surfaceof the mesh substrate and an upper portion of the molded body wherebythe intermediate material layer resides proximate to the at least oneexposed mesh substrate region, wherein the intermediate layer comprisesa plurality of spaced apart pieces of a material that is resorbable or aresorbable material with a plurality of spaced apart apertures thatprovides the at least one exposed region in the mesh substrate.
 5. Amolded orthopaedic implant comprising at least one mesh substrate havinga thickness of between about 0.5 mm to about 5 mm, having opposing upperand lower primary surfaces, wherein at least a major portion of the meshsubstrate lower primary surface is integrally moldably attached to amolded primary implant body, wherein the mesh substrate has at least oneselectively exposed region devoid of molded material associated with themolded primary implant body that exposes a portion of an outermostsurface of the mesh substrate to at least a partial thickness of themesh substrate so as to allow for tissue in-growth in the at least oneexposed region of the mesh substrate, and wherein the at least one meshsubstrate outermost surface has regions that include the molded materialassociated with the primary implant body, and further comprising atleast one temporary material that resides on an outermost portion of theupper primary surface of the mesh substrate and is removed prior toimplantation or resorbed in situ to define the at least one exposedregion.
 6. An implant according to claim 5, wherein the molded implantcomprises molded PVA hydrogel, and wherein the temporary materialcomprises moldable silicone that is peelably removable from the meshsubstrate.
 7. A molded orthopaedic implant comprising at least one meshsubstrate having a thickness of between about 0.5 mm to about 5 mm,having opposing upper and lower primary surfaces, wherein at least amajor portion of the mesh substrate lower primary surface is integrallymoldably attached to a molded primary implant body, wherein the meshsubstrate has at least one selectively exposed region devoid of moldedmaterial associated with the molded primary implant body that exposes aportion of an outermost surface of the mesh substrate to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate, andwherein the at least one mesh substrate outermost surface has regionsthat include the molded material associated with the primary implantbody, wherein the molded implant comprises molded PVA hydrogel, andwherein the implant further comprises at least one temporary materialthat resides on portions of the upper primary surface of the meshsubstrate and is resorbable in situ to define the selectively exposedregions.
 8. A molded orthopaedic implant comprising at least one meshsubstrate having a thickness of between about 0.5 mm to about 5 mm,having opposing upper and lower primary surfaces, wherein at least amajor portion of the mesh substrate lower primary surface is integrallymoldably attached to a molded primary implant body, wherein the meshsubstrate has at least one selectively exposed region devoid of moldedmaterial associated with the molded primary implant body that exposes aportion of an outermost surface of the mesh substrate to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate, andwherein the at least one mesh substrate outermost surface has regionsthat include the molded material associated with the primary implantbody, wherein the molded implant comprises molded PVA hydrogel, whereinthe implant further comprises at least one removable mesh peel layerresiding on the upper primary surface of the mesh substrate, the meshpeel layer comprising a resorbable biocompatible salt, and wherein themesh peel layer is removable from the molded implant prior toimplantation to expose the at least one exposed region in the meshsubstrate.
 9. A molded orthopaedic implant comprising at least one meshsubstrate having a thickness of between about 0.5 mm to about 5 mm,having opposing upper and lower primary surfaces, wherein at least amajor portion of the mesh substrate lower primary surface is integrallymoldably attached to a molded primary implant body, wherein the meshsubstrate has at least one selectively exposed region devoid of moldedmaterial associated with the molded primary implant body that exposes aportion of an outermost surface of the mesh substrate to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate, andwherein the at least one mesh substrate outermost surface has regionsthat include the molded material associated with the primary implantbody, wherein the mesh substrate comprises a knitted polyester fabric,and wherein the at least one selectively exposed region is a pluralityof spaced apart selectively exposed regions on the upper and lowersurfaces of the implant.
 10. A molded orthopaedic implant comprising atleast one mesh substrate having a thickness of between about 0.5 mm toabout 5 mm, having opposing upper and lower primary surfaces, wherein atleast a major portion of the mesh substrate lower primary surface isintegrally moldably attached to a molded primary implant body, whereinthe mesh substrate has at least one selectively exposed region devoid ofmolded material associated with the molded primary implant body thatexposes a portion of an outermost surface of the mesh substrate to atleast a partial thickness of the mesh substrate so as to allow fortissue in-growth in the at least one exposed region of the meshsubstrate, and wherein the at least one mesh substrate outermost surfacehas regions that include the molded material associated with the primaryimplant body, wherein the mesh substrate is a polyester mesh, andwherein the at least one selectively exposed region is a plurality ofspaced apart selectively exposed regions on the upper and lower surfacesof the implant.
 11. A molded orthopaedic implant comprising at least onemesh substrate having a thickness of between about 0.5 mm to about 5 mm,having opposing upper and lower primary surfaces, wherein at least amajor portion of the mesh substrate lower primary surface is integrallymoldably attached to a molded primary implant body, wherein the meshsubstrate has at least one selectively exposed region devoid of moldedmaterial associated with the molded primary implant body that exposes aportion of an outermost surface of the mesh substrate to at least apartial thickness of the mesh substrate so as to allow for tissuein-growth in the at least one exposed region of the mesh substrate, andwherein the at least one mesh substrate outermost surface has regionsthat include the molded material associated with the primary implantbody, wherein the implant is a spinal disc replacement implant that hasa plateless, non-articulating unitary solid body of crystallinehydrogel, and wherein the at least one mesh substrate is at least threemesh substrates integrally molded to the implant body, a first piece ofmesh material disposed about an annulus outer surface of the body, asecond piece of mesh material covering at least a portion of thesuperior surface of the body, and a third piece of mesh materialcovering at least a portion of an inferior surface of the body, whereinthe second and third pieces have a lesser thickness than the annuluspiece, and wherein the second and third pieces both comprise a pluralityof the selectively exposed regions, with the selectively exposed regionsbeing spaced apart regions on the outermost surface that are separatedby mesh regions filled with moldable material on the outermost surface,wherein the selectively exposed regions are configured to allow fortissue in-growth.